Pacemaker for spasmodic dysphonia

ABSTRACT

A stimulation system and method for treating to a human subject having spasmodic dysphonia includes a sensing electrode configured to detect voice activity of a vocalizing muscle of the subject and to generate a first signal, and a processor configured to receive the first signal from the sensing electrode and to generate at least one stimulation parameter based on the first signal. The system further includes a mechanical actuator configured to receive the stimulation parameter from the processor and to activate a glottic closure reflex of the subject in response to the stimulation parameter and a stimulating electrode configured to receive the stimulation parameter from the processor and stimulate the recurrent laryngeal nerve or the vagus nerve of the subject based on the stimulation parameter.

CROSS REFERENCE TO RELATED APPLICATIONS

The present application is a continuation of U.S. patent applicationSer. No. 13/708,111 filed Dec. 7, 2012, which claims priority to U.S.Provisional Patent Application No. 61/567,664 filed Dec. 7, 2011 andU.S. Provisional Patent Application No. 61/567,666 filed Dec. 7, 2011,the disclosures of which are incorporated by reference herein in theirentirety.

U.S. patent application Ser. No. 13/708,111 is also related to U.S.patent application Ser. No. 13/708,129 filed on Dec. 7, 2012 and U.S.patent application Ser. No. 13/708,146 filed on Dec. 7, 2012, thedisclosures of which are incorporated by reference herein in theirentirety.

TECHNICAL FIELD

The present invention relates to the treatment of spasmodic dysphonia,and in particular, to devices and methods for stimulating the recurrentlaryngeal nerve (RLN) or the glottic closure reflex of a human subjectto treat the spasmodic dysphonia.

BACKGROUND ART

Voicing occurs when air is expelled from the lungs through the glottis,creating a pressure drop across the larynx. When this drop becomessufficiently large, the vocal folds start to oscillate. The minimumpressure drop required to achieve phonation is called the phonationthreshold pressure, and for humans with normal vocal folds, it isapproximately 2-3 cm H₂O. The motion of the vocal folds duringoscillation is mostly laterally, though there is also some superiorcomponent as well. However, there is almost no motion along the lengthof the vocal folds. The oscillation of the vocal folds serves tomodulate the pressure and flow of the air through the larynx, and thismodulated airflow is the main component of the sound of most voicedphones.

The vocal folds will not oscillate if they are not sufficiently close toone another, are not under sufficient tension or under too much tension,or if the pressure drop across the larynx is not sufficiently large. Inlinguistics, a phone is called voiceless if there is no phonation duringits occurrence. In speech, voiceless phones are associated with vocalfolds that are elongated, highly tensed, and placed laterally (abducted)when compared to vocal folds during phonation.

Fundamental frequency, the main acoustic cue for the percept pitch, canbe varied through a variety of means. Large scale changes areaccomplished by increasing the tension in the vocal folds throughcontraction of the cricothyroid muscle. Smaller changes in tension canbe effected by contraction of the thyroarytenoid muscle or changes inthe relative position of the thyroid and cricoid cartilages, as mayoccur when the larynx is lowered or raised, either volitionally orthrough movement of the tongue to which the larynx is attached via thehyoid bone. In addition to tension changes, fundamental frequency isalso affected by the pressure drop across the larynx, which is mostlyaffected by the pressure in the lungs, and will also vary with thedistance between the vocal folds. Variation in fundamental frequency isused linguistically to produce intonation and tone.

The voicing mechanism that is specifically designed for voice productionis the larynx. The larynx is between the pharynx and the trachea. Itcommunicates with the mouth and the nose though the laryngeal and oralparts of the pharynx. Although the larynx is part of the air passages,the larynx normally acts as a valve for preventing swallowed food andforeign bodies from entering the lower respiratory passages. The larynxis located in the anterior portion of the neck.

The laryngeal skeleton comprises nine cartilages that are joined byvarious ligaments and membranes. Three of the cartilages are single(thyroid, cricoid and epiglottis), and three are paired (arytenoid,corniculate, and cuneiform).

The extrinsic muscles of the larynx move the larynx as a whole. Theinfrahyoid muscles (omohyoid, sternohyoid, and sternothyroid) aredepressors of the hyoid bone and the larynx, whereas the suprahyoidmuscles (stylohyoid, digastric, mylohyoid and geniohyoid) and thestylopharyngeus are elevators of the hyoid bone and larynx.

The intrinsic muscles of the larynx are concerned with the movements ofthe laryngeal parts, making alterations in the length and tension of thevocal folds and in the size and shape of the rima glottidis in voiceproduction. All intrinsic muscles of the larynx are supplied by therecurrent laryngeal nerve (RLN), a branch of the vagus nerve (CN X)except the cricothyroid muscle, which is supplied by the externallaryngeal nerve.

The adductors of the vocal folds include the lateral cricoarytenoidmuscles which arise from the lateral portions of the cricoid cartilageand insert into the muscular processes or the arytenoid cartilages.These muscles pull the muscular processes anteriorly, rotating thearytenoid cartilages so that their vocal processes swing medially. Thesemovements adduct the vocal folds and close the rima glottidis.

The principle abductors of the vocal folds are the posteriorcricoarytenoid muscles. These muscles arise on each side from theposterior surface of the lamina of the cricoid cartilage and passlaterally and superiorly to insert into the muscular processes of thearytenoid cartilages. They rotate the arytenoid cartilages, therebydeviating them laterally and widening the rima glottidis.

The main tensors of the vocal folds are the triangular cricothyroidmuscles. These are located on the external surface of the larynx betweenthe cricoid and thyroid cartilages. The muscle on each side arises fromthe anterolateral part of the cricoid cartilage and inserts into theinferior margin and anterior aspect of the inferior horn of the thyroidcartilage. These muscles tilt the thyroid cartilage anteriorly on thecricoid cartilage, increasing the distance between the thyroid andarytenoid cartilages. As a result, the vocal ligaments are elongated andtightened and the pitch of the voice is raised.

The principle relaxers of the vocal folds are the broad thyroarytenoidmuscles. They arise from the posterior surface of the thyroid cartilagenear the median plane and insert into the anterolateral surfaces of thearytenoid cartilages. One band of its inferior deep fibers, called thevocalis muscle, arises from the vocal ligament and passes to the vocalprocess of the arytenoid cartilages anteriorly. The thyroarytenoidmuscles pull the arytenoid cartilages anteriorly, thereby slackening thevocal ligaments. The vocalis muscles produce minute adjustments of thevocal ligaments (e.g., as occurs during whispering). They also relaxparts of the vocal folds during phonation and singing.

The laryngeal nerves are derived from the vagus nerve (CN X) through thesuperior laryngeal nerve and the RLN. All intrinsic muscles, exceptcricothyroid, are innervated by the RLN with fibers from the accessorynerve (CN XI). The external laryngeal nerve supplies the cricothyroidmuscle. The supraglottic portion of the laryngeal mucosa is supplied bythe internal laryngeal nerve, a branch of the superior laryngeal nerve.The infraglottic portion of the laryngeal mucosa is supplied by the RLN.

Dystonia is a movement disorder that can affect a single muscle group orthe entire body. Dystonia is typically characterized by sustainedmuscular contraction that is forceful and inappropriate. Althoughdystonia has been linked to malfunction in certain areas of the brain,such as the basal ganglia, the precise cause of the disease remainsunknown. Dystonias are generally classified into two groups, generalizedand focal. Generalized (non-focal) dystonia involves a large number ofmuscle groups. Focal dystonia involves a single muscle group. The mostcommon types of focal dystonia are blepharospasm, torticollis, writer'scramp, and laryngeal. Laryngeal dystonia, also called spasmodicdysphonia, is a focal, primary dystonia, affecting the muscles of thelarynx.

Spasmodic dysphonia is an extremely disabling form of dystonia that isoften misdiagnosed. Patients with spasmodic dysphonia have severelydiminished vocal capacity. The voice can range from strangled andpressed to breathy and barely perceptible.

SUMMARY OF EMBODIMENTS

In accordance with one embodiment of the invention, a method of treatinga human subject having spasmodic dysphonia includes providing a sensingelectrode configured to detect voice activity of the subject and togenerate a first signal and generating at least one stimulationparameter, using a processor, in response to receiving the first signal.The stimulation parameter is based on the first signal. The methodfurther includes activating a glottic closure reflex of the subject inresponse to the stimulation parameter.

In related embodiments, the sensing electrode may be configured todetect electromyographic (EMG) activity of a vocalizing muscle and/or todetect movement related to voice production. The sensing electrode maybe a microphone that detects acoustic signals related to voiceproduction, may be an impedance sensor that detects changes ofimpedances related to voice production, and/or may be a pressure sensorthat detects changes in pressure related to voice production. Theactivating may include providing a current pulse having a duration ofabout 0.01 msec to 20 msec and a magnitude in the range of about 0.05 mAto 20 mA. The stimulation parameter may include a stimulation frequencythat is approximately reciprocal to a contraction time of a vocal cordadductor of the subject and may include a stimulation frequency that isabove a reciprocal of a contraction time of a vocal cord abductor of thesubject. The stimulation parameter may include a stimulation voltagethat is above a threshold for activation of vocal cord abductor oradductor muscles of the subject. Alternatively, the stimulationparameter may include a stimulation voltage that is above a thresholdfor activation of vocal cord adductor muscles of the subject and below athreshold for activation of vocal cord abductor muscles of the subject.The stimulation parameter may include a stimulation voltage that isabove a threshold for activation of vocal cord abductor muscles of thesubject and above a threshold for activation of vocal cord adductormuscles of the subject. The stimulation parameter may include astimulation voltage so that a net force for activation of adductormuscles is higher than a net force for activation of abductor muscles ofthe subject. The method may further include determining when the voiceactivity has reached a predetermined level, and then having the sensingelectrode generate the first signal when the predetermined level isreached.

In accordance with another embodiment of the invention, a pacemaker fora human subject having spasmodic dysphonia includes a sensing electrodefor detecting voice activity of a vocalizing muscle of the subject andgenerating a first signal. The pacemaker also includes a processor forreceiving the first signal from the sensing electrode and generating atleast one stimulation parameter, the stimulation parameter based on thefirst signal. The system further includes a mechanical actuatorconfigured to receive the stimulation parameter from the processor andto activate a glottic closure reflex of the subject based on thestimulation parameter and a stimulating electrode configured to receivethe stimulation parameter and to activate the recurrent laryngeal nerveor the vagus nerve of the subject based on the stimulation parameter.

In related embodiments, the stimulating electrode may be a nerve cuffelectrode and/or a rod electrode. The stimulation electrode may beconfigured to provide a range of stimulation voltages. The processor maybe configured to detect when the first signal has reached apredetermined level and may be configured to generate the stimulationparameter when the predetermined level is reached. The mechanicalactuator may provide mechanical stimulation and the stimulationelectrode may provide electrical stimulation.

In accordance with a further related embodiment, the processor maydetect when the first signal has reached a predetermined level andrespond by generating the stimulating signal. Additionally, theprocessor may include a pulse generator. In accordance with otherrelated embodiments, the electrodes may be bipolar and/or tripolar. Thestimulating signal may be a biphasic current pulse which may have aduration of about 0.001 ms to 50 ms, in most subjects from 0.1 msec to 5msec, and a magnitude in the range of about 0.05 mA to 20 mA, in mostsubjects from 0.5 mA to 5 mA.

In accordance with related embodiments, the method may further includeproviding an energy coupling circuit that inductively couples energythrough the skin of the subject. The method may include providing anenergy coupling circuit that optically couples energy through the skinof the subject. Stimulating the vocalizing nerve of the subject with anelectrical signal may include stimulating the nerve with an electricalsignal at a frequency that is approximately reciprocal to thecontraction time of the vocal cord adductor of the subject. Stimulatingthe vocalizing nerve of the subject with an electrical signal mayinclude stimulating the nerve with an electrical signal at a frequencythat is above the reciprocal of the contraction time of the vocal cordabductor of the subject.

BRIEF DESCRIPTION OF THE DRAWINGS

The foregoing features of the invention will be more readily understoodby reference to the following detailed description, taken with referenceto the accompanying drawings, in which:

FIG. 1 is a graphical illustration of the underlying principle offrequency-dependent movement of the vocal cords in accordance with anembodiment of the present invention;

FIG. 2 is a graphical illustration of the frequency-dependent motion ofthe vocal cords in accordance with the embodiment of FIG. 1;

FIG. 3 is an illustration of a stimulation system for spasmodicdysphonia, in accordance with an embodiment of the invention, and FIG.3A is an exploded view of the circled region in FIG. 3;

FIG. 4 is a flow chart illustrating a method for stimulating avocalizing nerve in a human subject having spasmodic dysphonia inaccordance with an embodiment of the invention;

FIG. 5 is a flow chart illustrating a method for pacing laryngealactivity of a human subject having spasmodic dysphonia in accordancewith an embodiment of the invention; and

FIG. 6 is a flow chart illustrating a method for pacing laryngealactivity of a human subject using a manual activator in accordance withan embodiment of the invention.

DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

Spasmodic dysphonia is a central disease in which muscle spindlesresiding within the adductor and abductor muscles normally “report” tothe brain the voltage state of their respective muscular tissue by useof afferent nerve signals. If these spindles are damaged or impairedthey “report” the wrong signals and, consequently, the brain sends wrongnerve signals back, by use of efferent nerve fibers, to the peripheralanatomical structures, the adductor and abductor muscles. Typically, theimpairment causes a spasm-like behavior of the vocal folds, e.g., likestuttering. Thus, even though the nerve and corresponding muscle arefunctional and intact, the end result is that both vocal folds areclosed spasm-like.

There are two prominent types among a variety of different forms ofspasmodic dysphonia: abductory spasmodic dysphonia and adductoryspasmodic dysphonia. In abductory spasmodic dysphonia a spasm-likebehavior of the abductor muscles occurs whereas in adductory spasmodicdysphonia a spasm-like behavior of the adductor muscles occurs.

Embodiments of the present invention recognized the benefit of treatingspasmodic dysphonia by stimulating the RLN or vagus nerve or byactivating the glottic closure reflex by electrical and/or mechanicalstimulation in order to selectively activate the abductor muscle, theadductor muscles or both. The advantages of nerve stimulation or reflexactivation over intramuscular stimulation are less interference of thestimulation electrode from movement of the muscle, the placement of theimplanted electrode is distant from the risky, delicate location ofnerve muscle endplates, less invasive surgery is required for implantingthe stimulation electrode, etc.

The benefits of using embodiments of the present invention allow theopening and closing of the vocal folds to be activated by the samestimulation electrode based on the stimulation parameters selected dueto the differences between the abductor (the opener) and the adductor(the closer) muscles (e.g., frequency-dependent, different thresholds ordifference of net forces of adductor and abductor muscles). Exploitingthese differences allows for a stimulation system that provides for theselective activation of vocal fold closing muscles, without activationof vocal fold opening muscles, the selective activation of vocal foldopening muscles, without activation of vocal fold closing muscles,and/or the tensioning of vocal folds by graded balanced activation ofboth opening and closing muscles. In addition, activation of the vocalfolds closure has the effect of (1) glottis closure during episodes ofabductory spasmodic dysphonia and glottis opening during episodes ofadductory spasmodic dysphonia, (2) reducing the spasmodic effects byconditioning/relaxing activation of the spasmodic muscle, and (3)reducing the spasmodic effects by inhibiting spasmodic muscle byactivating the (non-spasmodic) antagonistic muscle of the spasmodicmuscle.

Embodiments of the present invention are directed to a system and methodof sensing the vocal activity of a vocalizing muscle contraction in thelarynx and/or pharynx and stimulation of the RLN or vagus nerveinnervating the vocalizing muscle, e.g., without the electricalstimulation of the muscle fibers directly, based on the sensed activity.This would allow the surgeon to choose the optimum accessibility to thenerve. In contrast, U.S. Pat. No. 5,111,814 by Goldfarb, incorporatedherein by reference, teaches sensing of electrical activity of normallyfunctioning muscle tissue and stimulating of reinnervated muscle tissueof the larynx.

Embodiments of the present invention are also directed to a system andmethod of sensing the vocal activity of a vocalizing muscle contractionin the larynx and/or pharynx and activating the glottic closure reflex.This reflex may be activated by stimulation of a nerve, such as thesuperior laryngeal nerve, the internal or external superior nerve,and/or the glossopharyngeal nerve. It may also be elicited bystimulating mechanoreceptors and/or mucosa of the larynx and/or pharynx,or by the slap reflex. Stimulation may occur by electric currents and/orby mechanical movement or vibration. This variety of stimulation sitesmay allow a surgeon to choose the optimum treatment for the patient. Theglottic closure reflex, in turn, activates the natural fiber tissuewhich innervates the vocalizing muscles that control the closure of thevocal folds.

In spasmodic dysphonia, it may be beneficial to stimulation the RLN orvagus nerve and to activate the glottic closure reflex at the same time.For example, the RLN or vagus nerve may stimulate the opening muscleswhile the glottic closure reflex activates the closing muscles.Operating both systems at the same time might allow for better controlof the counteracting signals. In addition, mechanical stimulation of theglottic closure reflex and electrical stimulation of the RLN or vagusnerve may be advantageous in order to avoid interference of twoelectrical stimulation signals. However, electrical stimulation of boththe glottic closure reflex and RLN may be used because the locations ofstimulation are separated. In either case, two stimulators may be used,e.g., one for electrical stimulation (e.g., stimulation electrode) andone for mechanical stimulation (e.g., mechanical actuator).

In some embodiments, the system and method may further include a sensingelectrode configured to sense the electrical activity of a vocalizingmuscle contraction in the larynx and/or pharynx and stimulating the RLNor vagus nerve innervating the vocalizing muscle, or activating theglottic closure reflex, based on the sensed activity. In this case, theglottis is closed by active electrical sensing/stimulation or electricalsensing and electrical/mechanical stimulation in order to increase thequality of the voice. In contrast, U.S. Pat. No. 5,111,814 is employedto stimulate muscles which open the glottis in order to increase theamount of inspired air. Similarly, US Patent Publication No. 2006/282127by Zealear, incorporated herein by reference, is employed to open thevocal folds for the same reason. Thus, embodiments of the present methodand device are directed to the sensing activity of vocalizing musclecontraction and not respiratory muscle contraction as, e.g., in USPatent Publication No. 2006/282127 by Zealear.

In some embodiments, a manual activator may be used, rather than asensing electrode, that senses a vocalizing muscle contraction. Themanual activator activates the RLN, the vagus nerve, or glottic closurereflex, e.g., by causing stimulation parameters to be sent to theappropriate locations via the stimulation electrode(s). The manualactivator allows the stimulation system to be inactive during periods inwhich vocalization would not be needed, e.g., during sleep or whileeating, but allows it to be manually activated when vocalization isdesired.

After active sensing of the vocalizing muscle contraction or manualactivation, various stimulation parameters may be used in order to takeadvantage of the differences between the abductor (the opener) and theadductor (the closer) muscles in terms of the threshold voltage foractivation, the contraction time, and the number of fibers. Thus, thestimulation parameters include varying amplitude, frequency and/orthreshold. For example, the applied voltage and the stimulationfrequency may be chosen such that the desired muscles are activated. Ingeneral, the stimulation voltage should be directly proportional to thethreshold values and the stimulation frequency indirectly proportionalto the contraction times.

Embodiments of the present invention may use the frequency-dependentmovement of the vocal cords, as shown in FIG. 1. Such movement occurs asa result of the difference in contraction times between the abductor andadductor muscles. The contraction time of the only existing abductor ofthe vocal cords, the posterior cricoarytenoid (PCA) muscle, issignificantly longer than that of the adductor muscles. The RLN containsthe nerve fibers to all muscles that act on the vocal cords (except thecricothyroid (CT) muscle which is innervated by the superior laryngealnerve (SLN)), randomly distributed over the whole nerve. Consequently,an action potential generated by an electrical stimulation alwaysreaches both abductor and adductor muscles. Thus, the glottis firstcloses due to the faster adductors, then it opens, and ends withrelaxation which leads to a vibration of the vocal cords.

When stimulated at a frequency approximately reciprocal to thecontraction time of the vocal cord abductor, the action potentialsarrive at the muscles at a time when the adductor muscles will have justrelaxed from the last activation when the next pulse arrives (as shownbelow the zero-line on the graph). The abductor, in contrast, has justreached its maximal contraction when the incoming initiation for thenext contraction causes their temporal summation (shown above thezero-line). Consequently, resulting tetanic abductor tension overcomesthe weaker single twitch adduction.

For stimulation at a frequency approximately reciprocal to thecontraction time of the vocal cord adductor, the adductor muscles alsoreach tetanic contraction, and due to their greater number (4:1) thevocal cords are closed.

Embodiments of the present invention may use the different thresholdsfor selective activation of the nerves innervating the abductor andadductor muscles. The threshold for activation for abduction is higherthan the threshold for adduction because the contraction time of the PCAmuscle is significantly longer than that of the adductor muscles.Therefore, the PCA muscle is innervated by nerve fibers of smaller meannerve fiber diameter which have a threshold for electrical activationhigher than for nerve fibers of higher mean nerve fiber diameter, suchas innervating the adductor muscles.

When stimulated by a stimulation voltage above the threshold foractivation of the nerve fibers innervating the adductor muscle but belowthe threshold for activation of the nerve fibers innervating theabductor muscle, the abductor muscle fibers will not be activated andtherefore relaxed. In contrast, nerve fibers innervating the adductormuscle fibers will be activated, leading to a contraction of theadductor muscles, and the vocal cords will close. When the stimulationvoltage is above the respective thresholds for activation for bothabductor and adductor muscles, then both sets of muscles will bestimulated. The larger the stimulation amplitude (i.e., the injectedamount of charge), the stronger both the abductor and adductor musclesare activated independent of the chosen stimulation frequency, providedthe stimulation voltage is above each respective threshold.

Embodiments of the present invention may use the difference of netforces of adductor and abductor muscles due to electrical activation forthe nerves innervating the abductor and adductor muscles. The net forcefor activation of adductor muscles is higher than the net force foractivation of abductor muscles due to their greater number (4 adductormuscles versus 1 abductor muscle per side).

When stimulated by a stimulation voltage above the threshold foractivation of the nerve fibers innervating the adductor muscles andabove the threshold for activation of the nerve fibers innervating theabductor muscle, the abductory (vocal fold opening) net force of theabductor muscle fibers will be lower than the adductory (vocal foldclosing) net force of the adductor muscle fibers, as a sum of forcesleading to a closing of the vocal folds.

Thus, the stimulation parameters should be selected based on the desiredapplication and selective activation. In summary, when the stimulationvoltage is below the threshold value for activation of the adductors,then no stimulation occurs regardless of the stimulation frequency oramplitude used. When the stimulation voltage is above the thresholdvalue for activation of the adductors, but below the threshold value foractivation of the abductors, then the vocal folds are closed, regardlessof the stimulation frequency or amplitude used, which should benefitabductory spasmodic dysphonia. When the stimulation voltage is above thethreshold value for activation of the abductors (and thus above thethreshold value for activation of the adductors as well), then the vocalfolds may be opened or opening due to tetanic contraction of theabductor muscle when the stimulation frequency is approximately thestimulation frequency of the abductor muscle and the amplitude is low orhigh, which should compensate for adductory spasmodic dysphonia. If aneven higher amplitude is used such that the force of tetanicallycontracted abductor muscle is less than the twitch contractions of theadductor muscles, then the vocal folds may be closing (although theremay be a ripple or vibration depending on the stimulation frequency)because the higher applied amplitude overrules tetanic contraction ofthe abductor muscle. When the stimulation voltage is above the thresholdvalue for activation of the abductors and the stimulation frequency isapproximately the stimulation frequency of the adductor muscle, then thevocal folds are closed, regardless of the amplitude used, which shouldcompensate for abductory spasmodic dysphonia. For example, depending onthe stimulation parameters, a low amplitude may be less thanapproximately 1.5 mA, a high amplitude may be about 1 to 3 mA, and avery high amplitude may be greater than about 2.5 mA, for a pulseduration of about 0.5 ms.

Consequently, based on the stimulation parameters used (such asdescribed above, as well as other combinations), there may be variousswitching scenarios for the adductor and abductor muscles that arebeneficial to selectively activate the vocalizing muscles in order toexercise or train the muscles. For example, with the selection of astimulation frequency approximately equal to the stimulation frequencyof the abductor muscle, a low amplitude, and a stimulation voltagegreater than the stimulation voltage for the adductor muscles, thestimulation voltage may be switched between a voltage less than thestimulation voltage of the abductor muscle to a stimulation voltagegreater than the stimulation voltage of the abductor muscle, whichcauses the vocal cords to switch between a closed and an open state.Similarly, with the selection of a stimulation frequency approximatelyequal to the stimulation frequency of the abductor muscle and thestimulation voltage to greater than the stimulation voltage for theabductor muscles, the amplitude may be switched between a low value anda high value (or very high value), which causes the vocal cords toswitch between an opened and an opening (or closing) state. Likewise,with the selection of a stimulation frequency approximately equal to thestimulation frequency of the abductor muscle and a low amplitude, thestimulation frequency may be switched between the stimulation frequencyof the abductor muscle and the adductor muscles, which causes the vocalcords to switch between an opened and a closed state.

Embodiments of the present invention include stimulation electrode(s)that are configured to provide various stimulation voltages, frequenciesand/or amplitudes, so that the various stimulation parameters may beimplemented.

In embodiments of the present invention, the RLN or vagus nerve isstimulated directly or indirectly (via the glottic closure reflex), andthe muscle is not simulated directly, because more than 10 times lesspower is necessary for activation of a nerve than of the muscle itself.Additionally, a nerve-cuff-electrode can be positioned along the nervefar from moving muscles and tissue and far from sensitive receptors,which would produce unwanted reactions.

FIG. 2 is a graphical illustration of the frequency-dependent motion ofthe vocal cords. Stimulation at 10 to 30 Hz causes a graded abduction201 of the vocal cords. Above 30 Hz graded cord adduction occurs 202,with total airway occlusion 203 at 100 Hz by bilateral stimulation.

FIGS. 3 and 3A are illustrations of a stimulation system according toone embodiment of the present invention. The stimulation system forspasmodic dysphonia includes one or more stimulating (efferent)electrodes 301 and may include one or more sensing (afferent) electrodes(not visible) or a manual activator that may be activated by the user,e.g., a switch or toggle, instead of, or in addition to, the sensingelectrodes. The stimulation system also includes a processor 303, whichmay include a pulse generator. The processor 303 may be implanted in thepatient's chest, and the stimulating electrodes 301 may be wrappedaround or placed near or in contact with the vagus nerve or RLN 302along with the electrode leads 304 and safety loops 305. Alternatively,the stimulation electrodes 301 may be used indirectly to stimulate theRLN or vagus nerve by activating the glottic closure reflex, bystimulation of a nerve, such as the superior laryngeal nerve, theinternal or external superior nerve, and/or the glossopharyngeal nerve.The stimulation electrodes 301 may be used to stimulate the glotticclosure reflex by stimulating mechanoreceptors and/or mucosa of thelarynx and/or pharynx, or by the slap reflex. As mentioned above, thestimulation may be electrical and/or mechanical or vibratorystimulation.

Embodiments of the present system may be totally or partially implantedin a human subject. For example, the stimulator may include a housingthat can be very small with all of the implant's electronic componentscontained in a robust and compact hermetically sealed case. Energy andnecessary information may be inductively or optically transferredthrough the skin of the subject. This can be achieved by eitherenclosing the electronic circuitry inside a metallic case with asecondary coil placed aside or around the case. Similarly, this may beachieved by enclosing the electric circuitry and a secondary coil insidea dielectric case.

Referring also to FIG. 4, the optional sensing (afferent) part of theclosed loop system may include one or more sensing electrodes thatdetect the voice activities of the infrahyoidal muscles or signalsrecorded by the alternative sensors (step 101). For example, the sensingelectrode(s) may be configured to detect electromyographic (EMG)activity of a vocalizing muscle and/or to detect movement related tovoice production. The sensing electrode may be a microphone that detectsacoustic signals related to voice production, an impedance sensor thatdetects changes of impedances related to voice production, and/or apressure sensor that detects changes in pressure related to voiceproduction. The sensing electrode may generate a first signal inresponse to the activity that has been detected.

The first signal is received (step 102) at a processor 303. Theprocessor 303 may include a pulse generator. The processor 303 receivesthe first signal from the sensing electrode and generates at least onestimulation parameter (step 103) that is based on the first signal. Thestimulation parameter or second signal may be a biphase current pulse,and the biphase current pulse may have a duration of about 0.001 ms to50 ms, in most subjects from about 0.1 msec to 5 msec, and a magnitudein the range of about 0.05 mA to 20 mA, in most subjects from about 0.5mA to 5 mA.

The stimulation parameter from the processor 303 is received by one ormore stimulating electrodes 301 (step 104), and the stimulatingelectrode(s) 301 stimulate a vocalizing nerve, such as the RLN or thevagus nerve directly (from which the RLN originates and which is easierto handle surgically), in accordance with the stimulation parameter.Alternatively, the stimulating electrode(s) 301 may stimulate the RLN orthe vagus nerve indirectly by activating the glottic closure reflex(es)(step 105), which then activate the RLN or vagus nerve. In accordancewith an embodiment of the invention, the stimulation is limited to thetime periods of voice production or swallowing or valsalva maneuver.Outside these activities, the synkinetic reinnervated vocal foldpassively relaxes to the paramedian position.

The stimulating electrodes and the sensing electrodes may be eitherbipolar or tripolar. Similarly, one electrode may be bipolar and oneelectrode may be tripolar. The electrode leads 304 should besufficiently damage-resistant. The lead body should be arranged in away, so that the nerve and the stimulator are influenced as little aspossible by movements of the muscles, the neck and the head.

Embodiments can be used to activate the vocal cord adduction in patientswith spasmodic dysphonia by stimulating the whole innervating RLN oralternatively, the vagus nerve, from which the RLN originates. Thistreatment is effective with respect to patients having spasmodicdysphonia because it is based on muscle characteristics and not on nerveor muscle/nerve characteristics only.

FIG. 5 is a flow chart illustrating a method of training therapy of ahuman subject in accordance with one embodiment of the invention.Electrical activity of a vocalizing muscle (such as the infrahyoidalmuscles) of a human subject is sensed (step 110), and a vocalizing nerve(such as the RLN or the vagus nerve) of the subject is directlystimulated with an electrical signal based on the sensed electricalactivity. Alternatively, after electrical activity is sensed, the RLN orthe vagus nerve may be indirectly stimulated by the activation of theglottic closure reflex(es) (step 120). The stimulation/activationparameters may include stimulating the RLN or vagus nerve with anelectrical signal at a stimulation frequency above the reciprocal valueof the contraction time of the vocal cord adductor of the subject.Stimulating the vocalizing nerve of the subject with an electricalsignal may include stimulating the nerve with an electrical signal at afrequency approximately reciprocal to the contraction time of the vocalcord adductor of the subject and above the reciprocal of the contractiontime of the vocal cord abductor of the subject.

FIG. 6 is a flow chart illustrating a method of pacing laryngealactivity of a human subject using a manual activator in accordance withone embodiment of the invention. The stimulation system is manuallyactivated in step 130. The manual activator may send a first signal tothe processor 303, which may include a pulse generator. The processor303 receives the first signal from the manual activator and generates atleast one stimulation parameter that is based on the first signal. Aglottic closure reflex is then activated (step 140) based on thestimulation parameter, which in turn stimulates the RLN or vagus nerveof the subject. The stimulation may be electrical and/or mechanical orvibratory stimulation.

Some embodiments of the processor 303 may be implemented as hardware,software (e.g., a computer program product), or a combination of bothsoftware and hardware. For example, embodiments may be implemented as acomputer program product for use with a computer system. Suchimplementation may include a series of computer instructions or programcode fixed either on a tangible medium, such as a computer readablemedium (e.g., a diskette, CD-ROM, ROM, or fixed disk) or transmittableto a computer system, via a modem or other interface device, such as acommunications adapter connected to a network over a medium. The mediummay be either a tangible medium (e.g., optical or analog communicationslines) or a medium implemented with wireless techniques (e.g.,microwave, infrared or other transmission techniques). The series ofcomputer instructions may embody all or part of the functionalitypreviously described herein with respect to the processor. Those skilledin the art should appreciate that such computer instructions may bewritten in a number of programming languages for use with many computerarchitectures or operating systems. Furthermore, such instructions maybe stored in any memory device, such as semiconductor, magnetic, opticalor other memory devices, and may be transmitted using any communicationstechnology, such as optical, infrared, microwave, or other transmissiontechnologies. It is expected that such a computer program product may bedistributed as a removable medium with accompanying printed orelectronic documentation (e.g., shrink wrapped software), preloaded witha computer system (e.g., on system ROM or fixed disk), or distributedfrom a server or electronic bulletin board over the network (e.g., theInternet or World Wide Web).

While the invention has been described in connection with specificembodiments thereof, it will be understood that it is capable of furthermodification. This application is intended to cover any variation, uses,or adaptions of the invention and including such departures from thepresent disclosure as come within known or customary practice in the artto which the invention pertains.

What is claimed is:
 1. A pacemaker system for a human subject havingspasmodic dysphonia, the system comprising: a sensing electrodeconfigured to detect voice activity of the subject and to generate afirst signal; a processor, in communication with the sensing electrode,configured to receive the first signal and to generate at least onestimulation parameter based on the first signal in order to activate aglottic closure reflex and to stimulate a recurrent laryngeal nerve orvagus nerve of the subject; a mechanical actuator configured to receivethe at least one stimulation parameter and to activate the glotticclosure reflex of the subject based on the at least one stimulationparameter; and a stimulating electrode configured to receive the atleast one stimulation parameter and to activate the recurrent laryngealnerve or the vagus nerve of the subject based on the at least onestimulation parameter.
 2. The system according to claim 1, wherein thestimulating electrode is a nerve cuff electrode, a rod electrode orcombinations thereof.
 3. The system according to claim 1, wherein thestimulation electrode is configured to provide a range of stimulationvoltages.
 4. The system according to claim 1, wherein the sensingelectrode is configured to detect electromyographic (EMG) activity of avocalizing muscle.
 5. The system according to claim 1, wherein thesensing electrode is configured to detect movement related to voiceproduction.
 6. The system according to claim 1, wherein the sensingelectrode is a microphone that detects acoustic signals related to voiceproduction.
 7. The system according to claim 1, wherein the sensingelectrode is an impedance sensor that detects changes of impedancesrelated to voice production.
 8. The system according to claim 1, whereinthe sensing electrode is a pressure sensor that detects changes inpressure related to voice production.
 9. The system according to claim1, wherein the at least one stimulation parameter includes a stimulationfrequency that is approximately reciprocal to a contraction time of avocal cord adductor of the subject.
 10. The system according to claim 1,wherein the at least one stimulation parameter includes a stimulationfrequency that is above a reciprocal of a contraction time of a vocalcord abductor of the subject.
 11. The system according to claim 1,wherein the at least one stimulation parameter includes a stimulationvoltage that is above a threshold for activation of a vocal cordabductor muscle of the subject.
 12. The system according to claim 1,wherein the at least one stimulation parameter includes a stimulationvoltage that is above a threshold for activation of vocal cord adductormuscles of the subject.
 13. The system according to claim 1, wherein theat least one stimulation parameter includes a stimulation voltage thatis above a threshold for activation of vocal cord adductor muscles ofthe subject and below a threshold for activation of a vocal cordabductor muscle of the subject.
 14. The system according to claim 1,wherein the at least one stimulation parameter includes a stimulationvoltage that is above a threshold for activation of a vocal cordabductor muscle of the subject and above a threshold for activation ofvocal cord adductor muscles of the subject.
 15. The system according toclaim 1, wherein the at least one stimulation parameter includes astimulation voltage so that a net force for activation of adductormuscles is higher than a net force for activation of an abductor muscleof the subject.
 16. The system according to claim 1, wherein theprocessor is configured to detect when the first signal has reached apredetermined level, and configured to generate the at least onestimulation parameter when the predetermined level is reached.